{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T13:18:15Z","timestamp":1784985495327,"version":"3.55.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,8]]},"abstract":"<jats:p>\n                    To unravel the heterogeneity and molecular signature of effector memory Th2 cells (Tem2), we analyzed 23 individuals\u2019 PBMCs of filaria-infected (Filaria\n                    <jats:sup>+<\/jats:sup>\n                    ) and 24 healthy volunteers (Filaria\n                    <jats:sup>\u2013<\/jats:sup>\n                    ), with or without coincident house dust mite (HDM) allergic sensitization. Flow cytometry revealed 3 CD4\n                    <jats:sup>+<\/jats:sup>\n                    Tem subsets \u2014 CCR4\n                    <jats:sup>+<\/jats:sup>\n                    CCR6\n                    <jats:sup>+<\/jats:sup>\n                    CRTH2\n                    <jats:sup>\u2013<\/jats:sup>\n                    Tem17, CCR4\n                    <jats:sup>+<\/jats:sup>\n                    CCR6\n                    <jats:sup>-<\/jats:sup>\n                    CRTH2\n                    <jats:sup>+<\/jats:sup>\n                    Tem2, and CCR6\n                    <jats:sup>+<\/jats:sup>\n                    CCR4\n                    <jats:sup>+<\/jats:sup>\n                    CRTH2\n                    <jats:sup>+<\/jats:sup>\n                    Tem17.2 \u2014 markedly enriched in Filaria\n                    <jats:sup>+<\/jats:sup>\n                    individuals. These subsets were sorted and analyzed by multiomic single-cell RNA immunoprofiling. SingleR-annotated Th2 cells from Tem2 and Tem17.2 cell subsets had features of pathogenic Th2 effector cells based on their transcriptional signatures, with downregulated\n                    <jats:italic>CD27<\/jats:italic>\n                    and elevated expression levels of\n                    <jats:italic>ITGA4<\/jats:italic>\n                    ,\n                    <jats:italic>IL17RB<\/jats:italic>\n                    ,\n                    <jats:italic>HPGDS<\/jats:italic>\n                    ,\n                    <jats:italic>KLRB1<\/jats:italic>\n                    ,\n                    <jats:italic>PTGDR2<\/jats:italic>\n                    ,\n                    <jats:italic>IL9R<\/jats:italic>\n                    ,\n                    <jats:italic>IL4<\/jats:italic>\n                    ,\n                    <jats:italic>IL5<\/jats:italic>\n                    , and\n                    <jats:italic>IL13<\/jats:italic>\n                    genes. When the Filaria\n                    <jats:sup>+<\/jats:sup>\n                    individuals were subdivided based on their allergic status, Tem2 cells in HDM\n                    <jats:sup>+<\/jats:sup>\n                    Filaria\n                    <jats:sup>+<\/jats:sup>\n                    individuals showed an overall reduction in TCR diversity, suggesting the occurrence of antigen-driven clonal expansion. Moreover, HDM\n                    <jats:sup>+<\/jats:sup>\n                    Filaria\n                    <jats:sup>+<\/jats:sup>\n                    individuals showed not only an expansion in the frequency of both Tem2 and Tem17.2 cell subsets, but also a change in their molecular program by overexpressing\n                    <jats:italic>GATA3<\/jats:italic>\n                    ,\n                    <jats:italic>IL17RB<\/jats:italic>\n                    ,\n                    <jats:italic>CLRF2<\/jats:italic>\n                    , and\n                    <jats:italic>KLRB1<\/jats:italic>\n                    , as well as increased antigen-induced IL-4, IL-5, and IL-13 production, suggesting that aeroallergens reshape the transcriptional and functional programming of Th2 cell subsets in human filarial infection toward a pathogenic immunophenotype.\n                  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